Design, Synthesis and Evaluation of 3-Substituted Coumarin Derivatives as Anti-inflammatory Agents

Abstract

Coumarin moiety has garnered momentous attention especially in the design of compounds with significant biological activities. In this work, a series of 3-substituted coumarin derivatives 6a-6l were synthesized and fully characterized. Most of the compounds could obviously inhibit the activity of COX-1 at the concentration of 10 μM.Besides, 6h and 6l exhibited highest inhibitory effects against COX-2 with inhibition rates of 33.48% and 35.71%, respectively. Detailed structure-activity relationships (SARs) were also discussed. In vivo studies, 6b, 6i and 6l could remarkably repress the xylene-induced ear swelling in mice at the dose of 20 mg/kg. Especially, 6l seemed to be the most effective compound at the dose of 10 mg/kg, displaying favorable anti-inflammatory activity comparable to indomethacin. All of these findings suggested that 6l might be utilized as a candidate for the treatment of inflammatory diseases.

Trending Topics on Coumarin and Its Derivatives in 2020

“…In other cases, the anti-inflammatory activity found for coumarin esters ( Figure 4 , general structure XVIII ) as inhibitors of the Kallikrein-related peptidase 9 (KLK9) involved in inflammatory processes of the skin is reported [ 31 ]. Finally, the replacement of the carboxylic group by a sulfone or sulfoxide group ( Figure 4 , general structure XIX ) gives rise to new inhibitors of cyclooxygenase-2 (COX-2) with activities comparable, in many cases, to indomethacin [ 32 ].…”

Coumarin: A Valid Scaffold in Medicinal Chemistry

“…In addition, at the dose of 20 mg/kg, the active molecules 21, 22, 23, 24, 25 and 26 could obviously repress ear swelling in vivo. Principally, molecule 26 exhibit satisfactory inhibitory activity like indomethacin at the dose of 10 mg/kg [70].…”

Coumarin-Based Compounds as Inhibitors of Tyrosinase/Tyrosine Hydroxylase: Synthesis, Kinetic Studies, and In Silico Approaches

“…Among the tyrosinase inhibitors, several authors have described the role of secondary plant metabolites, especially phenolic derivatives [ 24 , 25 , 26 ], including coumarins or 2 H -1-benzopyran-2-one, which are chemically characterized by the presence of a benzene ring fused to an α -pyrone [ 27 ]. This class of secondary metabolites arouses great interest in the academic community due to their vast pharmacological applications [ 28 , 29 , 30 , 31 ], such as their antitumor activities toward various cancer lineages [ 32 , 33 , 34 , 35 ], including human colon cancer (HCT-116) and human adenocarcinoma (HeLa) [ 36 ], and also their properties as anti-melasma agents and tyrosinase inhibitors [ 37 , 38 ]. As some examples ( Figure 1 ), we can highlight the studies performed by Pintus et al and Matos et al, who synthesized a series of heteroarylcoumarins and evaluated their inhibitory activities on mushroom tyrosinase, identifying compounds 1 and 2 as the most promising tyrosinase inhibitors [ 39 , 40 , 41 ].…”